Biomedical subjects

Diederick E Grobbee

Publications and source records attributed to Diederick E Grobbee.

At least 91 records · Page 5Linked to original sources

PubMed2005

Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study.

OBJECTIVE: Isoflavone supplementation in high doses is associated with plasma lipid, glucose and insulin levels. Little is known about the effects of intake within the range of western diets on these endpoints. DESIGN: We conducted a population-based cross-sectional study in 301 women aged 60-75 years. METHODS: Dietary isoflavone and lignan intake was assessed with a food frequency questionnaire covering habitual diet during the year preceding enrollment. The outcome measures were total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), fasting glucose and insulin levels. Data were analysed using linear regression and logistic regression models. In the analyses we adjusted for a wide range of potential confounders. RESULTS: High intake of isoflavones was associated with lower Lp(a) levels (tertile three versus tertile one: odds ratio 0.36, 95% CI 0.16; 0.80). No relation was found between blood levels and the other plasma lipids, glucose or insulin was found. CONCLUSION: The results of this study suggest that an effect of dietary phytoestrogen intake at low levels on plasma lipid levels is of limited magnitude. It is premature to advise postmenopausal women with low phytoestrogen intake to change their diet towards a phytoestrogen rich diet with the sole aim to prevent cardiovascular disease.

Aged↗

PubMed2005

High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

BACKGROUND: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a potential confounder. METHODS: An observational study was performed in 215 subjects with type 1 diabetes treated with multiple insulin injection therapy. Atherosclerosis was assessed by measurement of carotid intima-media thickness (CIMT). RESULTS: The cumulative dose of regular insulin showed a positive and significant relation with CIMT: increase of 21 microm in CIMT per S.D. of insulin use (95% CI: 8-35 adjusted for gender and age), which remained unchanged after adjustment for duration of diabetes, HbA1c, BMI, pulse pressure, physical activity and carotid lumen diameter. A similar relation was found for intermediate-acting insulin: 15.5 microm per S.D. (2-29), which was no longer present after further adjustment. CONCLUSIONS: These findings provide evidence that a high cumulative dose of regular insulin is a risk factor for atherosclerosis.

Adult↗

PubMed2005

Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at 4 years.

BACKGROUND: The relationship between mite and pet allergen exposure in infancy and the subsequent development of sensitization and asthma is complex. OBJECTIVE: We prospectively investigated the effect of allergen exposure at 3 months of age on the development of sensitization, wheeze, and physician-diagnosed asthma in the first 4 years of life in a birth cohort of children with and without an atopic mother. METHODS: Children participated in the Prevention and Incidence of Asthma and Mite Allergy study. Allergen exposure at 3 months of age was determined from mattress dust samples. Specific IgE to inhalant allergens was measured at 4 years of age, and information about wheeze and physician-diagnosed asthma was collected with yearly questionnaires. RESULTS: Mite and cat allergen exposure in infancy were associated with an increased risk of specific sensitization to house dust mite and cat, respectively, at 4 years of age. There were borderline significant associations between cat allergen exposure and persistent wheeze in the total study population and between dog allergen exposure and persistent wheeze in children with a nonatopic mother. In children with an atopic mother, there was some indication of a positive association between mite allergen exposure and physician-diagnosed asthma. CONCLUSION: Early house dust mite and cat allergen exposure might lead to sensitization and, in case of cat allergen exposure, to persistent wheeze. Early mite and dog allergen exposure might lead to asthma and persistent wheeze, respectively, but only in subgroups defined by maternal atopy.

Adult↗

PubMed2005

Hospital-related determinants for surgical-site infection following hip arthroplasty.

OBJECTIVE: To determine hospital-related risk factors for surgical-site infection (SSI) following hip arthroplasty. DESIGN: Prospective, multicenter cohort study based on surveillance data and data collected through a structured telephone interview. With the use of multilevel logistic regression, the independent effect of hospital-related characteristics on SSI was assessed. SETTING: Thirty-six acute care hospitals in the Dutch surveillance network for nosocomial infections (PREZIES), from 1996 to 2000. PATIENTS: Thirteen thousand six hundred eighty patients who underwent total or partial hip arthroplasty. RESULTS: A high annual volume of operations was associated with a reduced risk of SSI (risk-adjusted risk ratio [RR] per 50 extra operations, 0.85; 95% confidence interval [CI95], 0.74-0.97). With each extra full-time-equivalent infection control staff member per 250 beds available for prevention of SSI, the risk for SSI was decreased (RR, 0.48; CI95, 0.16-1.44), although the decrease was not statistically significant. Hospital size, teaching status, university affiliation, and number of surgeons and their years of experience showed no important association with the risk of SSI. CONCLUSION: Undergoing surgery in a hospital with a low volume of operations increases a patient's risk of SSI.

Adult↗

PubMed2005

Randomized controlled trial of the effects of soy protein containing isoflavones on vascular function in postmenopausal women.

BACKGROUND: The incidence of cardiovascular disease increases after menopause, possibly because of the decline in estrogen. Soy protein, a rich source of estrogen-like isoflavones, is hypothesized to improve vascular function. OBJECTIVE: The objective of this study was to investigate whether supplementation with soy protein, a rich source of estrogen-like isoflavones, improves vascular function. DESIGN: We performed a 12-mo double-blind randomized trial to compare the effects of soy protein containing 99 mg isoflavones/d (aglycone weights) with those of milk protein (placebo) on blood pressure and endothelial function in 202 postmenopausal women aged 60-75 y. RESULTS: Changes in endothelial function during the intervention were not significantly different between the soy and the placebo groups. After the intervention, systolic blood pressure increased in the soy group significantly more than it did in the placebo group; the difference in change was 4.3 mm Hg (95% CI: 0.3, 8.4 mm Hg; P = 0.04) for systolic blood pressure, but only 2.0 mm Hg (95% CI: -0.74, 4.71 mm Hg; P = 0.15) for diastolic blood pressure. In the soy group only, systolic and diastolic blood pressure decreased and endothelial function improved in the equol producers, whereas systolic and diastolic blood pressure increased and endothelial function deteriorated in the equol nonproducers. CONCLUSIONS: The results of this trial do not support the hypothesis that soy protein containing isoflavones have beneficial effects on vascular function in older postmenopausal women. Whether certain subgroups of women (eg, equol producers) do benefit from the intervention remains to be elucidated.

Aged↗

PubMed2005

Higher dietary intake of lignans is associated with better cognitive performance in postmenopausal women.

Data on the relation between phytoestrogens and cognitive function are still sparse. The purpose of this study was to examine the relation between the dietary intake of phytoestrogens and cognitive function in healthy postmenopausal women consuming a Western diet. We conducted a community-based survey among 394 postmenopausal women. Isoflavone and lignan intake was calculated from a validated FFQ. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Data were analyzed using logistic regression with intact cognitive function defined as a score >/= 26 as the outcome variable. After adjustment for confounders, increasing dietary lignans intake was associated with better performance on the MMSE [OR and (95%CI): 1.49 (0.94-2.38)]. Results were most pronounced in women who were 20-30 y postmenopausal [2.02 (1.11-3.71)]. Isoflavone intake was not related to cognitive function. From our results we conclude that higher dietary intake of lignans is associated with better cognitive function in postmenopausal women.

Aged↗

PubMed2005

Impact of anesthesia management characteristics on severe morbidity and mortality.

BACKGROUND: Quantitative estimates of how anesthesia management impacts perioperative morbidity and mortality are limited. The authors performed a study to identify risk factors related to anesthesia management for 24-h postoperative severe morbidity and mortality. METHODS: A case-control study was performed of all patients undergoing anesthesia (1995-1997). Cases were patients who either remained comatose or died during or within 24 h of undergoing anesthesia. Controls were patients who neither remained comatose nor died during or within 24 hours of undergoing anesthesia. Data were collected by means of a questionnaire, the anesthesia and recovery form. Odds ratios were calculated for risk factors, adjusted for confounders. RESULTS: The cohort comprised 869,483 patients; 807 cases and 883 controls were analyzed. The incidence of 24-h postoperative death was 8.8 (95% confidence interval, 8.2-9.5) per 10,000 anesthetics. The incidence of coma was 0.5 (95% confidence interval, 0.3-0.6). Anesthesia management factors that were statistically significantly associated with a decreased risk were: equipment check with protocol and checklist (odds ratio, 0.64), documentation of the equipment check (odds ratio, 0.61), a directly available anesthesiologist (odds ratio, 0.46), no change of anesthesiologist during anesthesia (odds ratio, 0.44), presence of a full-time working anesthetic nurse (odds ratio, 0.41), two persons present at emergence (odds ratio, 0.69), reversal of anesthesia (for muscle relaxants and the combination of muscle relaxants and opiates; odds ratios, 0.10 and 0.29, respectively), and postoperative pain medication as opposed to no pain medication, particularly if administered epidurally or intramuscularly as opposed to intravenously. CONCLUSIONS: Mortality after surgery is substantial and an association was established between perioperative coma and death and anesthesia management factors like intraoperative presence of anesthesia personnel, administration of drugs intraoperatively and postoperatively, and characteristics of delivered intraoperative and postoperative anesthetic care.

Aged↗

PubMed2005

Age at menopause, cause-specific mortality and total life expectancy.

BACKGROUND: A later menopause has been associated with a decreased cardiovascular risk but with an increased risk for breast and endometrial cancer. The net effect on mortality is unclear. We determined the association of age at menopause with longevity and with the balance between cardiovascular and cancer mortality. METHODS: We analyzed data from a breast cancer screening cohort comprising 12,134 postmenopausal women followed for an average of 17 years. We used Cox proportional hazards models and life tables to calculate the life expectancy of an average Dutch woman at age 50. RESULTS: During 204,024 person-years, there were 2607 deaths, of which 963 were due to cardiovascular diseases and 812 due to cancer. Ischemic heart disease risk decreased with a later menopause (hazard ratio [HR] = 0.98 per year; 95% confidence interval = 0.96-0.99), but the risk of fatal uterine or ovarian cancer increased (1.07 per year; 1.01-1.12). A later menopause was associated with longer overall survival; HR for total mortality was 0.98 per year (0.97-0.99). Life expectancy in women with menopause after age 55 was 2.0 years longer than those with menopause before age 40. Adjustment for potential confounders did not materially change the results. CONCLUSIONS: Age-adjusted mortality is reduced 2% with each increasing year of age at menopause. In particular, ischemic heart disease mortality is 2% lower. Although the risk of death from uterine or ovarian cancer is increased by 5%, the net effect of a later menopause is an increased lifespan.

Age Distribution↗

PubMed2005

Alcohol intake and aortic stiffness in young men and women.

BACKGROUND: Moderate alcohol consumption has been shown to protect against cardiovascular disease. Aortic stiffness can be regarded as a marker of cardiovascular disease risk. Previously we have shown an inverse to J-shaped association between alcohol intake and aortic stiffness in middle-aged and elderly men and postmenopausal women. OBJECTIVE: In the present study we examined whether a relation between alcohol intake and aortic stiffness is already present at a younger age. DESIGN: Cross-sectional data of a cohort study in men and women aged 28 years were analysed stratified by gender (240 men and 283 women). MEASUREMENTS: Alcohol intake was derived from a questionnaire and aortic stiffness was assessed by pulse-wave velocity measurement. RESULTS: In women an alcoholic beverage intake of >/=1 glass/day is associated with a 0.36 m/s (95% confidence interval, -0.58 to -0.14) lower pulse-wave velocity compared with non-drinkers. In men alcohol intake is also inversely related to pulse-wave velocity, but this was not significant. These findings were independent of age, blood pressure and heart rate. CONCLUSIONS: These findings suggest that moderate intake of alcohol may affect vascular stiffness at an early age, notably in women. These findings may be viewed as compatible with a vascular protective effect of alcohol that expresses well before the occurrence of symptomatic cardiovascular disease.

Adult↗

PubMed2005

Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials.

PURPOSE: Coffee is a widely consumed beverage and small health effects of substances in coffee may have large public health consequences. It has been suggested that caffeine in coffee increases the risk of hypertension. We performed a meta-analysis of randomized controlled trials of coffee or caffeine and blood pressure (BP). DATA IDENTIFICATION: BP trials of coffee or caffeine published between January 1966 and January 2003 were identified through literature databases and manual search. STUDY SELECTION: A total of 16 studies with a randomized, controlled design and at least 7 days of intervention was selected, comprising 25 strata and 1010 subjects. DATA EXTRACTION: Two persons independently obtained data on sample size, type and duration of intervention, changes in BP and heart rate (HR), and subjects' characteristics for each trial. Meta-analysis was performed using a random-effects model. RESULTS: A significant rise of 2.04 mmHg [95% confidence interval (CI), 1.10-2.99] in systolic BP and 0.73 mmHg (95% CI, 0.14-1.31) in diastolic BP was found after pooling of coffee and caffeine trials. When coffee trials (n = 18, median intake: 725 ml/day) and caffeine trials (n = 7, median dose: 410 mg/day) were analysed separately, BP elevations appeared to be larger for caffeine [systolic: 4.16 mmHg (2.13-6.20); diastolic: 2.41 mmHg (0.98-3.84)] than for coffee [systolic: 1.22 mmHg (0.52-1.92) and diastolic: 0.49 mmHg (-0.06-1.04)]. Effects on HR were negligible. CONCLUSIONS: Regular caffeine intake increases BP. When ingested through coffee, however, the blood pressure effect of caffeine is small.

Adult↗

PubMed2005

Serum levels of sex hormone-binding globulin (SHBG) are not associated with lower levels of non-SHBG-bound testosterone in male newborns and healthy adult men.

OBJECTIVE: It is generally accepted that SHBG decreases the bioavailability and activity of testosterone (T). In in vitro experiments increased levels of SHBG will be associated with decreased levels of non-SHBG bound testosterone (non-SHBG-T). However, in vivo SHBG can alter both production and clearance rates and thus plasma levels of T. DESIGN AND PATIENTS: In order to study the effect of SHBG on the levels of non-SHBG-T in vivo in the presence of an active hypothalamo-pituitary-gonadal (HPG) axis we conducted a cross sectional study in 400 healthy adult men with an age range of 40-80 years and in 106 newborn boys. MEASUREMENTS: In both groups, regression coefficients (beta) and partial correlation coefficients (r) were calculated for the relationship between SHBG and T or non-SHBG-T. Adult men were divided into age groups per decade (40-50 years, 51-60 years, 61-70 years and 71-80 years) to study possible differences in the impact of SHBG on the level of non-SHBG-T throughout ageing. RESULTS: Higher levels of SHBG were associated with higher levels of total testosterone in neonates (beta = 0.02 +/- 0.004, r = 0.44, P < 0.001) but not with non-SHBG-T (beta = -0.001 +/- 0.001, r = 0.05, P = 0.52). In adult men there was a significant age related increase in levels of SHBG and an age-related decrease of both total and non-SHBG-T. Higher SHBG was strongly associated with higher total testosterone in all age groups (beta = 0.26, 0.26, 0.26 and 0.23 for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively, P < 0.001 for all age groups). Higher SHBG was not or only slightly associated with higher non-SHBG-T beta = 0.02 (P = 0.32), beta = 0.04 (P = 0.03), beta = 0.04 (P = 0.02) and beta = 0.02 (P = 0.16) for 40-50 years, 51-60 years, 61-70 years and 71-80 years, respectively. CONCLUSIONS: In contrast to general belief, SHBG levels barely influence levels of non-SHBG-bound testosterone both in male newborns and healthy adult men: the influence, if any, is positive. Consequently the age related increase of SHBG does not account for the age related decline in non-SHBG-T in healthy adult men.

Adult↗

PubMed2005

Endogenous oestrogens are related to cognition in healthy elderly women.

OBJECTIVE: To investigate whether levels of endogenous hormones, in particular circulating oestrogens and SHBG, are associated with cognition in healthy postmenopausal women. DESIGN: Cross-sectional study. PATIENTS: Four hundred and two healthy postmenopausal women aged 50-74 years between 8 and 30 years after menopause, none taking oestrogen. MEASUREMENTS: Serum concentration of oestradiol, oestrone, and sex hormone binding globulin (SHBG) determined by immunoassay. Cognition assessed using the mini-mental state examination questionnaire (MMSE). RESULTS: In this group, 149 individuals had a MMSE score < 27, while only 89 individuals had a MMSE score < 26, indicating a relatively healthy population with regard to cognitive ability. Cognition decreased with age, time since menopause and blood pressure, and was better with higher age at menopause. Serum oestrogens and SHBG levels were not related to age, age at menopause, or time since menopause, and oestrogen levels were positively associated with blood pressure. After adjustment for mean arterial pressure and SHBG, the frequency of mild cognitive impairment decreased significantly with higher oestradiol and oestrone serum levels [ORs Q5 vs. Q1: 0.41 (95% CI 0.20-0.84) and 0.51 (95% CI 0.20-0.99) for oestradiol and oestrone, respectively]. CONCLUSIONS: Postmenopausal women with higher remaining circulating oestradiol levels appear less likely to suffer from cognitive impairment. This effect is independent of age at menopause, time since menopause and BMI. These findings support the hypothesis that endogenous oestrogens may protect against cognitive decline with ageing.

Adipose Tissue↗

PubMed2005

Predicting pressure ulcers: cases missed using a new clinical prediction rule.

AIM: The aim of this paper is to report a study describing patients with pressure ulcers that were incorrectly classified as 'not at risk' by the prediction rule and comparing them with patients who were correctly classified as 'not at risk'. BACKGROUND: Patients admitted to hospital are at risk of developing pressure ulcers. Although the majority of pressure ulcers can be predicted using a recently developed prediction rule, up to 30% of patients with pressure ulcers may still be misclassified. METHODS: Between January 1999 and June 2000 a prospective cohort study was conducted in two large hospitals in the Netherlands. Patients admitted to neurology, internal, surgical, and elder care wards for more than 5 days were included (n = 1229), and were examined weekly. Information on potential prognostic determinants for pressure ulcers mentioned in the literature was recorded. Outcome was defined as occurrence of a pressure ulcer grade 2 or worse during hospital admission. RESULTS: Patients who developed pressure ulcers experienced more problems with 'friction and shear' and underwent surgery more often and longer. Also, they were more often admitted because of malignant conditions. CONCLUSION: We found no specific characteristics that clearly distinguished patients with pressure ulcers that were incorrectly classified as 'not at risk' by the prediction rule from patients who were correctly classified as 'not at risk'. It appears difficult to improve further on the prediction of pressure ulcers using available clinical information.

Adolescent↗

PubMed2005

Cyp17, urinary sex steroid levels and breast cancer risk in postmenopausal women.

Endogenous sex hormones play an important role in the etiology of breast cancer. Polymorphisms in genes encoding for enzymes involved in steroidogenesis may therefore play a role in breast cancer risk. Cytochrome P450c17alpha (Cyp17) functions at key branch points in human steroidogenesis. A T-->C transition (A1 and A2 allele) in the 5' untranslated region may be associated with increased expression of Cyp17. Using a case-cohort design, we studied the effects of the A2 allele on endogenous sex hormone levels and breast cancer risk within a large population-based cohort (n = 9,349) in the Netherlands (the DOM-cohort). Cyp17 genotype was determined in 335 incident postmenopausal breast cancer cases, which occurred after follow-up (median time to follow-up, 19 years) of the entire cohort, and in a random sample of 373 women (subcohort). Concentrations of estrone (E1), estradiol (E2), testosterone, 5alpha-androstane-3alpha, 17beta-diol (3alphaD), and creatinine were measured in first-morning urine samples. Only among women with body mass index (BMI) < 25 kg/m2 was the A2A2 genotype associated with higher levels of E1, E2, and 3alphaD compared with a group of women with either the A1A1 or the A1A2 genotype (e.g., geometric means of E(1) in ng/mg(creatinine): A2A2, 2.23; A1A1/A1A2, 1.47; P = 0.03). Adjusted breast cancer rate ratios for women with the A1A2 or A2A2 genotype compared with women with the A1A1 genotype were 0.96 (0.68-1.37) and 0.80 (0.47-1.35), respectively. These results did not differ between women with low and high BMI. In conclusion, this paper shows that women with low BMI and the A2A2 genotype had higher endogenous sex steroid levels compared with women with the A1A1 genotype. However, these increased sex steroid levels are not translated into an increased breast cancer risk in these women.

Adult↗

PubMed2005

Postmenopausal breast cancer risk and cumulative number of menstrual cycles.

OBJECTIVE: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women. METHODS: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718). The cumulative number of menstrual cycles was computed in 6,031 (90%) women. We calculated the number of cycles until FFTP among parous participants. The number of menstrual cycles was impossible to compute in women who reported to be always irregular; therefore, we added the "always irregular" category in the analysis. During the 46,746 person-years of follow-up, 168 breast cancer cases were identified. Cox regression models were used and adjustments were made to account for potential confounders. RESULTS: Even when our data does not show a clear linear gradient, we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime. Using < or = 415 cycles as reference, the hazard ratio for the irregular group, 416-453, 454-490, and > or = 491 cycles was 1.11 (.56, 2.19), 1.88 (1.14, 3.12), 1.74 (1.05, 2.87), and 1.80 (1.09, 2.96), respectively. Although not statistically significant, and of less magnitude, the risk estimates for the number of cycles before FFTP showed the same tendency. CONCLUSION: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk.

Aged↗

PubMed2005

The 1944-1945 Dutch famine and subsequent overall cancer incidence.

Caloric restriction seems to be the most potent dietary intervention to protect against a variety of cancers in animals. We investigated whether overall cancer risk is affected in humans after exposure to a brief famine, followed by a period of abundance. We used data of approximately 15,000 women who were exposed at various degrees to the 1944-1945 Dutch famine at ages between 2 and 33 years. Between 1983 and 1986, these women were asked about their individual experiences of famine exposure ("absent," "moderate," or "severe exposure"). During follow-up until January 2000, 1,602 new cancer cases were identified by the regional cancer registry. We assessed the relation between famine and total cancer risk by weighted Cox regression models, in which a 15% random sample was used to represent person-years lived in the entire cohort. In these models, we adjusted for potential confounders. Overall cancer risk was increased in women having been severely famine exposed compared with women having been unexposed (hazard ratio, 1.25; 95% confidence interval, 1.01-1.55). Exclusion of breast cancer cases from our analyses showed that this increase in risk was largely driven by the previously reported increase in breast cancer risk: women who were severely exposed to the famine were at a 1.12 (95% confidence interval, 0.87-1.43) times increased risk of non-breast cancer compared with the unexposed. In conclusion, we found no indications that this brief famine has affected overall cancer risk, exclusive of breast cancer. Counteracting increased caloric intake following the famine, however, may have obscured any relation.

Adolescent↗

PubMed2005

Polymorphisms in the estrogen receptor alpha gene and mammographic density.

The presence of the PvuII or the XbaI polymorphism in the estrogen receptor alpha gene (ESR1, 6q25) has been related to breast cancer risk; however, results are not fully consistent. To further elucidate this relation, we examined these polymorphisms in relation with mammographic density, a measure of dense tissue in the breast, which is strongly associated with breast cancer risk. For this study, 620 participants aged 49 to 68 years were selected from the Prospect-European Prospective Investigation into Cancer and Nutrition cohort. Blood samples, lifestyle- and medical questionnaire data and mammograms were available for these women. Genotyping was done using the TaqMan PCR assay and mammographic density was assessed using a computer-assisted method. Means of mammographic density were compared by ESR1 genotypes and haplotypes. The percentage density was higher in women with one or two copies of the PvuII p allele (means for Pp and pp are 37% and 36%, respectively) than in those with the PP genotype (32%, P(trend) = 0.09). Women with one or two copies of the XbaI x allele had higher mean percentage density (Xx and xx, 36% and 37%, respectively) than those with the XX genotype (31%, P(trend) < 0.01). Haplotype 1 (px) was associated with increased density, whereas haplotype 2 (PX) was associated with decreased density, both suggesting an allele-dose effect (P(trend) = 0.08 and <0.01, respectively). Similar associations were found with absolute density (P(trend) < 0.01). The findings of this study support the view that ESR1 polymorphisms may affect breast cancer risk through differences in breast density.

Aged↗

PubMed2005

Measurements of breast density: no ratio for a ratio.

Breast density, as visible on mammograms, is generally assessed as the occupied percentage of the breast and is a risk factor for breast cancer. Various studies have looked into the causation and alteration of relative density but the relation of a determinant with a relative measure does not allow a direct etiologic interpretation. It was our goal to compare the effects of known determinants on relative density and the absolute amounts of dense and nondense tissues. We measured the absolute and relative densities in a population of 418 postmenopausal women participating in a breast cancer screening program. The occupied surface area was calculated after manually tracing the contours of the tissues on digitized mammograms. Information on determinants was available through physical examination and questionnaires. Data were analyzed by multivariate linear regression. Age and parity were found to decrease the amount of dense tissue and the ages at menarche and menopause were found to increase it (R(2) = 13%). The amount of nondense tissue was increased by higher body mass index (BMI), age, and parity (R(2) = 43%). Relative density was affected by a combination of these factors (R(2) = 29%) with directionalities of effects that are comparable to those of dense tissue. However, the magnitudes of these effects were the resultant of the effects on dense and nondense tissues. The influence of BMI on relative density was completely due to an effect on nondense tissue. Although relative density is a relevant prognostic factor, inferences about the etiology of breast density should be made on the basis of absolute measures.

Age Factors↗